This invention relates to a method and device for inducing localized hypothermia in tissue, specifically brain tissue that is at risk of necrosis due to stroke.
Stroke is a leading cause of death and disability. It is estimated that over 725,000 people suffer a major stroke in the United States each year, and that over 100,000 of these people die. There are two main categories of stroke: ischemic and hemorrhagic. A blockage in an artery in the brain causes ischemic stroke, and a rupture in an artery in the brain causes hemorrhagic stroke. There are approximately 600,000 ischemic stokes, and 125,000 hemorrhagic strokes in the United States each year.
Within the last decade there has been a marked increase in understanding why and how brain cells die from ischemic stroke. Cells within an infarction zone have dramatically reduced blood flow of 20% of normal or less. Cells within this infarction zone will be irreversibly damaged within a few minutes. Surrounding the infarcted zone is a volume of tissue called the xe2x80x9cischemic penumbraxe2x80x9d or xe2x80x9ctransitional zonexe2x80x9d in which blood flow is between 20% and 50% of normal. Cells in this area are endangered, but not irreversibly damaged. Ischemia in the infarction zone, and in the ischemic penumbra causes the ischemic cells to release excitatory proteins which migrate into surrounding tissues triggering a hyper metabolic response that leads to cell death beyond the infarction zone and the ischemic penumbra. This hyper metabolic response triggers inflammation, edema, local and global pyrexia, cerebral hypertension, apoptosis, and an increase in intra-cranial pressure causing a cascade of cell injury and death. This cascade of cell injury and death is referred to as secondary ischemic injury in the literature. Nowhere in the art is a mechanism described to that can effectively prevent or limit the migration of excitatory proteins from ischemic tissue, to surrounding normal tissue in the brain.
There is a growing body of research that shows that hypothermia is neuroprotective, however, the exact mechanisms are not fully understood. Schwab et al recently demonstrated that inducing systemic hypothermia following severe ischemic stroke provides a significant improvement in clinical outcome. Schwab treated 25 patients suffering from hemispheric stroke as a result of infarction of the middle cerebral artery with systemic hypothermia at 33 degrees centigrade for 48 to 72 hours. All patients were under full anesthesia during the period of hypothermia. The survival rate, and the clinical outcome of the survivors was significantly better than would otherwise have been expected. Schwab also demonstrated that critical elevations in intra-cranial pressure could be effectively reduced by systemic hypothermia following ischemic stroke.
However, there was a significant complication rate, unrelated to the stroke, but due to the depth and duration of systemic hypothermia Also, it took 3.5 to 6.2 hours for the body core temperature to reach the target therapeutic temperature of 33 degrees centigrade, and it took an average of 18 hours for the body temperature to return to normal after systemic cooling was withdrawn. All of the patients that died in this study did so as a result of a terminal rise in intra-cranial pressure during the rewarming period. Schwab notes, xe2x80x9cRewarming has to be considered the critical phase of hypothermia therapyxe2x80x9d.
Kammersgaard et al recently reported treating 17 patients suffering ischemic stroke with systemic hypothermia for 6 hours upon admission of the patient to the hospital. Unlike in the Schwab study, there was no body core temperature target; the patient was cooled by xe2x80x9cforced cold air methodxe2x80x9d for 6 hours and the core body temperature was monitored. At six hours the average core body temperature was 36.5 degrees centigrade. Kammersgaard reported that the hypothermia therapy was well tolerated by the patients, and did not require anesthesia. Also, there were no complications encountered due to the hypothermia therapy. However, the clinical outcome of patients studied showed no statically significant improvement in outcome over the historical controls used in this study.
Systemic hypothermia has historically been accomplished by immersion of the patient""s body in a cool bath. Today there are several commercial systemic hypothermia systems available. They consist of blankets or pads where cooled water is circulated through channels in the walls of the blanket or pad, and the patient""s body is maintained in intimate contact. Medivan Corp. manufactures an example of a modern hypothermia system under the trade name Arctic Sun Cooling System.
Systemic hypothermia has been demonstrated to be effective in improving the outcome of ischemic stroke, however, there are several drawbacks to this approach: 1) It takes several hours to lower a patient""s body to therapeutic temperatures. This delay in achieving therapeutic temperatures allows for the progression of irreversible injury to the brain. 2) The practical therapeutic hypothermic temperature and duration is limited by the ability of the patient to tolerate, or survive the therapy. 3) The side effects of systemic hypothermia are frequent and can be life threatening, especially in frail patients. Side effects include shivering, cardiac arrhythmia and arrest, pneumonia, infections, and coagulation disorders. 4) The target of hypothermia therapy is the zone around the cerebral infarction, therefore inducing hypothermia systemically places the patient at undue risk. 5) During the xe2x80x9ccritical phasexe2x80x9d (rewarming period) of hypothermia treatment, there is no effective way to manage a sudden and critical increase in intra-cranial pressure, since re-cooling the body to reverse the increase in intra-cranial pressure takes several hours. 6) Brain tissue in a zone of infarction, and in the transitional zone surrounding the infarction have substantially reduced blood perfusion rates, and brain tissues in a zone of infarction, and in the transitional zone surrounding the infarction are in a hyper-metabolic state, therefore heat generated by the hyper-metabolic processes inside the zone of infarction, and inside the transitional zone cannot be effectively dissipated by blood perfusion. This results in a temperature differential between the infarcted and transitional zone, and the surrounding normal tissue, where tissues in the infarcted and transitional zone are at a higher temperature than the surrounding normal tissue. Systemic hypothermia cools a zone of infarction and surrounding transitional zone from without, and therefore cannot eliminate this temperature differential.
There are several examples in the art where catheters are constructed with a cooling means which is placed into the carotid artery to cool the blood entering the head. This offers an advantage over systemic hypothermia, since it provides a means to cool the head to lower temperatures than the rest of the body, but it still results in systemic hypothermia. Also, since the scientific evidence suggests that hypothermia must be maintained for extended periods of time, there is a great risk that clots will form on the catheters and migrate into the brain leading to further episodes of stroke. The mechanism of cooling a zone of infarction in the brain, or the surrounding transitional zone with this approach is the same as with systemic hypothermia, and does not overcome the significant limitations as described above.
There are numerous examples of interstitial cooling probes in the art. Nowhere in the art is it suggested that interstitial cooling probes may be used to treat stroke, and nowhere in the art is there an example of a cooling probe that may be practically fixated to the head and left indwelling in the brain for the extended periods of time required for effective hypothermia treatment of stroke.
Therefore, it is an object of this invention to provide a method and apparatus for treating stroke. Another object of this invention is to provide a method and apparatus for treating ischemic stroke. A further object of this invention is to provide a means of reducing secondary ischemic injury in the brain following stroke.
In accordance with one aspect of this invention, stroke is treated by placement of an interstitial cooling probe in the brain, and then cooling the brain with the probe. In another aspect of this invention, stroke is treated by placement of an interstitial cooling probe in to a specific volume of brain tissue that is suffering ischemia due to stroke, and then cooling the ischemic volume of brain tissue with the probe, while otherwise maintaining normal body temperature in unaffected areas of the brain and the body. In accordance with another aspect of this invention, stroke is treated by placement of an interstitial cooling probe into an infarcted volume of brain tissue, then using the probe to cool the infarcted volume of tissue sufficiently to conduct heat from tissue surrounding the infarction into the infarction, thereby cooling the tissue surrounding the infarction. In accordance with another aspect of this invention, stroke is treated by placement of an interstitial cooling probe into an infarcted volume of brain tissue, then using the probe to freeze at least a portion of the infarcted volume of tissue, thereby arresting and/or retarding the migration of excitatory cellular protein from the infarcted volume, to brain tissues surrounding the infarcted volume for a period of time between one hour and one month. In accordance with another aspect of this invention, stroke is treated by placement of an interstitial cooling probe into an infarcted volume of brain tissue, then using the probe to freeze at least a portion of the infarcted volume of tissue thereby arresting and/or retarding the migration of excitatory cellular protein from the infarcted volume, to brain tissues surrounding the infarcted volume for a period of time sufficient for the innate healing response to surround and seal the infarcted volume by fibrosis. In accordance with another aspect of this invention, stroke is treated by placement of an interstitial cooling probe into an infarcted volume of brain tissue, then using the probe to cool the infarcted volume of tissue sufficiently to reduce the metabolic activity in tissue surrounding the infarcted volume. In accordance with another aspect of this invention, stroke is treated by placement of an interstitial cooling probe into an infarcted volume of brain tissue, and then cooling the infarcted volume of brain tissue to a predetermined temperature for a predetermined time. In accordance with another aspect of this invention, stroke is treated by placement of an interstitial cooling probe into an infarcted volume of brain tissue, and then cooling the infarcted volume of brain tissue to a predetermined temperature, where then the temperature is increased gradually over a period of time from the initial low temperature, to normal body temperature, with the period of time being greater than one hour and less than one month. In accordance with another aspect of this invention, stroke is treated by placement of an interstitial cooling probe into an infarcted volume of brain tissue, and then cooling the infarcted volume of brain tissue to a degree based on the physiological response to said cooling. In accordance with another aspect of this invention, apparatus for treating stroke includes an interstitial cooling probe constructed for placement into the brain by stereotaxic radiological guidance, where the distal tip of the probe includes a cooling mechanism with sufficient heat absorbing capability to cool a volume of brain tissue to the degree, and for a period of time sufficient to mitigate the effects of stroke. In another aspect of this invention, apparatus for treating stroke is an interstitial cooling probe where the distal end of the probe contains a mechanism for cooling tissue surrounding the distal tip of the probe, and a mechanism near the distal tip to sense an effect of said cooling. In another aspect of this invention, apparatus for treating stroke is an interstitial cooling probe constructed for an extended period of cooling and indwelling in the brain, with the period of cooling and indwelling being greater than one hour, and as long as one month.
Accordingly, besides the objects and advantages of the method and apparatus to treat stroke described in my patent above, several objects and advantages of the present invention are:
(a) to provide localized hypothermia to a volume of brain tissue at risk from stroke to the degree that offers maximum clinical benefit without inducing a hypothermia in areas of the brain or the body that are not at risk from stroke;
(b) to provide localized hypothermia to a volume of brain tissue surrounding a zone of infarction by removing heat from about the center of the infarction to a sufficient degree that the volume of tissue surrounding the infarction is cooled to the degree that has maximal clinical benefit;
(c) to provide localized hypothermia to a volume of brain tissue at risk from stroke where the method for inducing hypothermia takes advantage of the fact that tissue about the center of an infarction lacks perfusion, therefore providing an optimal medium for conducting heat from surrounding tissue.
(d) to provide localized hypothermia to a volume of brain tissue at risk from stroke where the method for inducing hypothermia takes advantage of the fact that tissue about the center of an infarction is dead or irreversibly injured, therefore providing a volume of tissue where otherwise lethal (to brain tissue) hypothermic temperatures (below 0 degrees centigrade) can be achieved without clinical consequence, allowing for a large volume of tissue to be cooled to clinically beneficial temperatures with a single small caliber cooling probe;
(e) to provide localized hypothermia to a volume of brain tissue at risk from stroke where the method for inducing hypothermia inherently produces a temperature profile in the volume of brain tissue at risk from stroke where tissues with lower blood perfusion rates are cooled to lower temperatures than tissues with higher blood perfusion rates; where tissues with lower blood perfusion rates are at greater risk of irreversible injury than tissue with higher blood perfusion rates, and where the neuroprotective effects of hypothermia increases as tissue temperature decreases, therefore providing greatest neuroprotective effects from hypothermia to brain tissues at greatest risk;
(f) to provide localized hypothermia to a volume of brain tissue at risk from stroke within a minimal time after patient presentation where therapeutic temperatures are achieved rapidly due to the fact that only the affected volume of the brain is cooled, and that the cooling probe may attain temperatures that are otherwise lethal to brain tissue (below 0 degrees centigrade) without clinical consequence;
(g) to provide localized hypothermia to a volume of brain tissue at risk from stroke where the degree of hypothermia is adjusted according to the physiological response to hypothermia, where the physiological response to hypothermia is a change in intra-cranial pressure;
(h) to provide localized hypothermia to a volume of brain tissue at risk from stroke where the degree of hypothermia is adjusted according to the physiological response to hypothermia, where the physiological response to hypothermia is a change in patient symptoms.
(i) to provide localized hypothermia to a volume of brain tissue at risk from stroke where the degree of hypothermia is adjusted according to the physiological response to hypothermia, where the physiological response to hypothermia is a change in localized blood perfusion;
(j) to provide localized hypothermia to a volume of brain tissue at risk from stroke where the degree of hypothermia is adjusted according to the physiological response to hypothermia, where the physiological response to hypothermia is a change in the size of the volume of infarcted tissue;
(k) to provide localized hypothermia to a volume of brain tissue at risk from stroke where the degree of hypothermia is adjusted according to the physiological response to hypothermia, where the physiological response to hypothermia is a change in blood chemistry.
(l) to provide apparatus for inducing localized hypothermia to a volume of brain tissue at risk from stroke according to the objectives stated above;
(m) to provide an interstitial brain cooling probe that is constructed to provide a cooling means at the distal tip;
(n) to provide an interstitial brain cooling probe that is constructed to be placed by stereotaxic radiological guidance by well known surgical methods;
(o) to provide an interstitial brain cooling probe that is constructed to provide for long term cooling and indwelling;
(p) to provide an interstitial brain cooling probe that is constructed to provide for fixation to the head of the patient;
(q) to provide an interstitial brain cooling probe that is constructed to provide for protection against infection;
(r) to provide an interstitial brain cooling probe that is constructed to provide for a means to sense a response to cooling;
(s) to provide an interstitial brain cooling probe that is constructed to provide for a means to control the degree of cooling applied to the surrounding brain tissue;
(t) to provide a system that includes an interstitial brain cooling probe, a control consol, and a means to connect the interstitial brain cooling probe to the control console.